title: Oral immunization with attenuated Salmonella carrying a co-expression plasmid encoding the core and E2 proteins of hepatitis C virus capable of inducing cellular immune responses and neutralizing antibodies in mice.
abstract: Hepatitis C virus (HCV) core protein has long been considered an attractive candidate for inclusion in a protective vaccine. However, this protein may hamper the development of systemic immune responses because of its immune suppressive properties. We previously reported that immune responses to HCV core protein could be efficiently induced by attenuated Salmonella carrying the HCV core protein, but not the HCV core DNA vaccine. To optimize the combination of the core protein and envelope protein 2 (E2) into a vaccine formulation to induce cellular immune responses and neutralizing antibodies, we constructed a plasmid containing two expression cassettes. One expression cassette was included to regulate the expression of HCV core protein by an inducible in vivo-activated Salmonella promoter, the other was included to regulate the expression of HCV E2 protein by the cytomegalovirus enhancer/promoter. Oral immunization of BALB/c mice with the attenuated Salmonella strain SL7207 carrying this plasmid efficiently induced HCV core and E2-specific cellular immune responses and antibodies. IgG purified from immunized mice could neutralize the infectivity of HCV pseudoparticles (HCVpp) of both the autologous Con 1 isolate and the heterologous H77 isolate, and cell culture produced HCV (HCVcc) of Con1-JFH1 chimera. These results indicated that this vaccine strategy can effectively deliver core and E2 protein to the immune system and provide a promising approach for the development of prophylactic and therapeutic vaccines against HCV infection.
authors.affiliation: Department of Microbiology, Shanghai Key Laboratory of Medical Biodefense, Second Military Medical University, Shanghai 200433, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Cao
authors.forename: Zhihui
authors.initials: Z
authors.lastname: Chen
authors.forename: Yanli
authors.initials: Y
authors.lastname: Ren
authors.forename: Yuan
authors.initials: Y
authors.lastname: Luo
authors.forename: Mingmei
authors.initials: M
authors.lastname: Cao
authors.forename: Wei
authors.initials: W
authors.lastname: Lu
authors.forename: Ping
authors.initials: P
authors.lastname: Zhao
authors.forename: Zhongtian
authors.initials: Z
authors.lastname: Qi
mesh_terms: D000284:Administration, Oral; D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood; D003587:Cytomegalovirus / Q000235:genetics; D000939:Epitopes / Q000235:genetics / Q000276:immunology*; D005822:Genetic Vectors / Q000235:genetics / Q000276:immunology; D057809:HEK293 Cells; D016174:Hepacivirus / Q000235:genetics / Q000276:immunology; D006526:Hepatitis C / Q000276:immunology / Q000517:prevention & control*; D018937:Hepatitis C Antibodies / Q000097:blood; D006801:Humans; D007111:Immunity, Cellular; D007371:Interferon-gamma / Q000032:analysis / Q000276:immunology; D015847:Interleukin-4 / Q000032:analysis / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D009500:Neutralization Tests; D010957:Plasmids / Q000235:genetics / Q000276:immunology; D011401:Promoter Regions, Genetic; D012475:Salmonella / Q000235:genetics / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014758:Viral Core Proteins / Q000276:immunology*; D014759:Viral Envelope Proteins / Q000276:immunology*; D014761:Viral Hepatitis Vaccines / Q000235:genetics / Q000276:immunology*
chemical_list: D057134:Antibodies, Neutralizing; D000939:Epitopes; D018937:Hepatitis C Antibodies; D014758:Viral Core Proteins; D014759:Viral Envelope Proteins; D014761:Viral Hepatitis Vaccines; C069130:nucleocapsid protein, Hepatitis C virus; C091015:glycoprotein E2, Hepatitis C virus; D015847:Interleukin-4; D007371:Interferon-gamma